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PubMedDate not supplied

Delta-sleep-inducing peptide stimulates melatonin, 5-methoxytryptophol and serotonin secretion from perifused rat pineal glands.

The pineal gland is known to synthesize numerous indolamines. Since delta-sleep-inducing peptide (DSIP, a tryptophan nonapeptide) is found in the pineal gland, its effect on the secretion of indolamines was investigated. DSIP stimulated melatonin (MEL), 5-methoxytryptophol (5-ML) and serotonin (5-HT) synthesis and release, whereas it did not affect pineal cyclic AMP levels. The stimulatory effect of DSIP on MEL secretion was dose dependent between 5 x 10(-6) and 10(-4) M, whereas the minimal effective concentration of DSIP on 5-ML secretion was higher than 10(-5) M. The effect of DSIP (10(-4) M) was compared to the effect of isoproterenol (ISO, 10(-6) M) on MEL and 5-HT release. ISO stimulated MEL secretion and concomitantly decreased 5-HT release. With regard to kinetic characteristics, the effect of DSIP (10(-4) M) on MEL release was faster and of shorter duration than the effect of ISO (10(-6) M; 2 and 4 h, respectively). At 10(-4) M, DSIP potentiated the ISO-induced increase of MEL secretion. The DSIP-stimulated release of MEL was not significantly altered when the pineal glands were treated with 10(-5) M propranolol (a beta-adrenergic antagonist), 10(-5) M prazosin (an alpha 1-adrenergic antagonist) or 10(-5) M naloxone (an opioidergic antagonist). This study demonstrates that the DSIP-induced secretion of indolamines from rat pineal glands may not be elicited through the well-known noradrenergic or opioid systems.

Animals↗

PubMed1976

Pineal gland calcification (PGC) in Ugandans. A radiological study of 200 isolated pineal glands.

Two hundred formalin-fixed pineal glands from consecutive unselected post-mortems on Ugandan Africans have been X-rayed. The degree of pineal gland calcification has been divided into four stages and it is shown that 43 per cent of all pineal glands after the age of ten years are likely to be detected in an ordinary skull X ray. This high percentage of calcification contrasts with the previously reported low figure from races other than whites. The pineal glands from females were more often calcified and heavier than those from males; however, the stalks of pineal glands from males were calcified more frequently than those of females. The average weight per decade was almost constant. In Ugandan Africans the pineal glands were significantly lighter than in Caucasians, and a possible reason for this is briefly discussed.

Adolescent↗

PubMed1985

Eyes--the second (and third) pineal glands?

The pineal gland, the retinas and perhaps other tissues as well may in some species produce melatonin that appears in significant quantities in the circulation. In at least one species, Japanese quail, the circadian rhythm in the levels of circulating melatonin reflects contributions from both the pineal and the retinas; in other species circulating melatonin may come exclusively from the pineal or perhaps only from the eyes. Comparative behavioural and physiological data from several bird and lizard species indicate that retinas and pineal glands fulfil similar endocrine roles. Current evidence suggests that in iguanid lizards either retinas or pineal glands, but not both in the same species, have important regulatory influences on circadian organization. This suggests that it should be relatively easy to influence the melatonin-forming ability of a tissue by natural selection, an interpretation bolstered by our finding that the ability to synthesize melatonin has been inadvertently eliminated in the pineal glands of laboratory mice, presumably by the selection involved in producing inbred strains. The genetics of melatonin synthesis in mice is briefly discussed.

Animals↗

PubMed2004

Retinal illumination phase shifts the circadian rhythm of serotonin N-acetyltransferase activity in the chicken pineal gland.

The pineal gland of birds, in contrast to its mammalian counterpart, is a directly photosensitive organ. It has recently been demonstrated that light also acting via the retina acutely suppresses melatonin synthesis in the chicken pineal gland. The present study was aimed to investigate whether retinal illumination alone was capable of resetting the biological oscillator generating the circadian rhythm of pineal serotonin N-acetyltransferase (AA-NAT) activity in the chicken. Ocular exposure of chickens to 6 h low intensity white light (4 lux) potently suppressed AA-NAT activity (the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway) in the pineal gland. In addition, this light pulse produced phase-dependent shifts in the circadian AA-NAT rhythm. Exposure to light early in the subjective night (circadian time (CT) 12-18) caused a phase delay in the circadian rhythm of pineal AA-NAT activity by 3.5+/-0.4 h compared to non-exposed controls. When the light pulse was applied during the second half of the subjective night (CT18-24), it produced a large phase advance of the circadian rhythm of pineal AA-NAT activity by 10.9+/-0.4 h. The advancing effect of light was more pronounced than the phase-delaying effect. Our results suggest that in the chicken retinally perceived light provides a powerful and important signal for synchronization of circadian rhythmicity in the pineal gland.

Adaptation, Biological↗

PubMed1987

Coexistence of central and peripheral benzodiazepine binding sites in the human pineal gland.

The pineal gland and particularly its major hormone, melatonin, may participate in several physiological functions, including sleep promotion, anticonvulsant activity and the modulation of biological rhythms and affective disorders. These effects may be related to an interaction with benzodiazepine receptors, which have been demonstrated to be present in the pineal gland of several species including man. The present study examined the characteristics of benzodiazepine binding site subtypes in the human pineal gland, using [3H]flunitrazepam and [3H]PK 11195 as specific ligands for central and peripheral type benzodiazepine binding sites respectively. Scatchard analysis of [3H]flunitrazepam binding to pineal membrane preparations was linear, indicating the presence of a single population of sites. Clonazepam and RO 15-1788, which have a high affinity for central benzodiazepine binding sites, were potent competitors for [3H]flunitrazepam binding in the human pineal, whereas RO 5-4864 had a low affinity for these sites. Analyses of [3H]PK 11195 binding to pineal membranes also revealed the presence of a single population of sites. RO 5-4864, a specific ligand for peripheral benzodiazepine binding sites was the most potent of the drugs tested in displacing [3H]PK 11195, whereas clonazepam and RO 15-1788 were weak inhibitors of [3H]PK 11195 binding to pineal membranes. Overall, these results demonstrate, for the first time, the coexistence of peripheral and central benzodiazepine binding sites in the human pineal gland.

Aged↗

PubMed2000

The presence of acetylcholinesterase-positive nerve fibres in the deep pineal gland and the pineal stalk but not in the superficial part of adult albino rats.

Application of the histochemical method for testing acetylcholinesterase (AChE, EC 3.1.1.7) showed the presence of AChE-positive nerve fibers in the deep pineal gland and the pineal stalk but not in the superficial part of adult albino rats. These findings may indirectly support the existence of the potentially cholinergic innervation of at least some of the rat pinealocytes present in these parts of the gland and augment the evidence of the heterogeneity of the rat pinealocytes. It is possible that cholinergic neurons in the medial habenular nuclei or in the parasympathetic sphenopalatine ganglion may be a source of these AChE-positive fibres. The examination was performed at the light microscope level.

Acetylcholinesterase↗

PubMed1976

Age-related changes in the intact and sympathetically denervated gerbil pineal gland.

The pineal gland of four-month-old gerbils contains numerous calcareous deposits (corpora arenacea or concretions). Also, the tissue appears vacuolated due to the presence of a number of large rounded spaces. The deposits are usually associated with or lying within these "vacuoles". By eight months of age, the number of both the corpora arenacea and the "vacuoles" are increased over those present in the pineals of four-month-old gerbils. Bilateral superior cervical ganglionectomy at one month of age prevents the formation of both the concretions and "vacuoles". The cells in the sympathetically denervated pineal glands are smaller than those in pineal glands of animals that possess intact superior cervical ganglia.

Aging↗

PubMed1981

Rhodopsin-like photosensitivity of isolated chicken pineal gland.

The pineal gland of lower vertebrates such as fish, amphibians and reptiles is primarily a photoreceptor organ and its electrical activity changes in response to environmental lighting, whereas the mammalian pineal gland is a secretory organ and no longer responds to direct illumination. It is uncertain whether the avian pineal gland retains a photoreceptive capability, and also whether the gland is a photosensor involved in the photo-periodic control of reproductive systems and circadian rhythms in birds. Recently, I and other workers have shown that the circadian rhythm of serotonin N-acetyltransferase activity persisted in organ cultures of chicken pineals, indicating the presence of an endogenous circadian oscillator in the gland. Also, the observation that direct illumination of cultured chicken pineals suppressed the night-time increase of N-acetyl-transferase activity suggests that the gland contains a photoreceptor. I report here that the action spectrum of the photosensitivity of the isolated chicken pineal resembles the absorption spectrum of rhodopsin.

Animals↗

PubMed1997

Stimulatory effect of bombesin on phosphoinositide metabolism in the rat pineal gland.

The pineal gland is under complex peptidergic nervous control originating from hypothalamic nuclei. The daily rhythm of bombesin-like peptide in the hypothalamus suggests that this neuropeptide, similarly as other neuropeptides, might be involved in modulation of the physiological activity of the pineal gland. In our experiments we studied the mechanism of signal transduction of bombesin in the isolated pineal glands of rats. The phosphoinositide signalling system was examined by measuring 32P-labelling of phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP) and phosphatidylinositol bisphosphate (PIP2), which reflects phosphoinositide cycle activation. Bombesin induced a significant increase in 32P-labelling of PI, PIP and PIP2. The antagonist of this neuropeptide, (D-Phe12-Leu14)-bombesin, suppressed the increase in 32P-labelling of all phosphoinositides. Bombesin was without effect on cAMP dependent protein phosphorylation. The data indicate that bombesin activates the PI signalling system via specific receptors.

Amino Acid Sequence↗

PubMed1999

Arginine vasotocin activates phosphoinositide signal transduction system and potentiates N-acetyltransferase activity in the rat pineal gland.

The pineal gland is innervated by pinealopetal peptidergic fibers originating in the hypothalamic nuclei which release arginine vasopressin (AVP) and arginine vasotocin (AVT) from their endings. Since the mechanism of AVT action on the pineal signal transduction and melatonin synthesis has not been determined so far, we examined the effect of AVT on the phosphoinositide signalling system and the N-acetyltransferase (NAT) activity in the rat pineal gland. The effect of AVP 4-9 fragment and AVP analogue desmopressin was also tested. The phosphoinositide signalling system was studied by measuring 32P labelling of phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP) and phosphatidylinositol bisphosphate (PIP2) which reflects PI cycle activation. AVT (10(-5) and 10(-4) M) induced a significant increase in 32P labelling of PI, PIP and PIP2. The AVT mediated activation of the PI signal cascade was supressed by the vasopressin V1 receptor antagonist. The desmopressin and AVP 4-9 fragment were without the effect on PI signalling. To assess the AVT role in the melatonin synthesis we studied the daily pattern of the pineal NAT activity in rats treated by AVT (10 microg/100 g b.w). AVT application in the dark period of the day significantly increased nocturnal NAT activity. It can be summarized that AVT activates PI signalling system and potentiates NAT activity in the rat pineal gland.

Animals↗

PubMed1991

Molecular and cellular aspects of hydroxyindole-O-methyltransferase expression in the developing chick pineal gland.

The pineal gland influences circadian activity and seasonal breeding through the production of an indolic hormone, melatonin. The terminal step of melatonin biosynthesis is catalyzed by hydroxyindole-O-methyltransferase (HIOMT). Using an antibody directed against HIOMT, we examined the differentiation of the melatoninergic phenotype in the developing chick pineal gland. HIOMT first appeared 4 days before hatch and rose linearly until the 7th day posthatch. This was correlated with an increased immunoreactivity of the 38 kDa enzyme on Western blots and with an accelerated rate of HIOMT biosynthesis as demonstrated by [35S]methionine labeling. Immunocytochemistry revealed a growing number of HIOMT-positive cells between day 2 before hatch and day 15 posthatch. Until hatching HIOMT was expressed almost exclusively in modified photoreceptors. Parafollicular pinealocytes became HIOMT-positive mostly after hatching. Their different timings of functional differentiation emphasize the existence of two populations of melatonin-producing cells in the chick pineal gland.

Acetylserotonin O-Methyltransferase↗

PubMed1979

Cytochemical studies on cytoplasmic granular elements in the hamster pineal gland.

The pineal gland of adult golden hamsters (Mesocricetus auratus) was studied by various cytochemical methods at the electron microscopic level: (1) the modified chromaffin reaction specific for 5-hydroxytryptamine (5-HT), (2) argentaffin reaction, (3) zinc-iodide-osmium (ZIO) mixture reaction and (4) acid phosphatase reaction. In the pinealocytes, the dense-cored vesicles (80-160 nm in diameter) show both chromaffinity and argentaffinity, while the population of dense bodies (150-400 nm in diameter) is reactive to ammoniacal silver solution and ZIO mixture but not to the modified chromaffin reaction. After incubation for demonstration of acid phosphatase activity, reaction products are localized in some, but not all, of the dense bodies, in some of the small vesicles in the Golgi region and in one or two inner Golgi saccules. In nerve fibers in the pineal gland, small granulated vesicles are also reactive to the modified chromaffin reaction and ZIO mixture. Based upon these cytochemical results the following conclusions have been reached: (1) dense cored vesicles in the pinealocytes and small granulated vesicles in the nerve fibers of the hamster pineal gland contain 5-HT, and (2) the population of dense bodies in the pinealocytes is heterogeneous, some are lysosomes and the other are possibly the granules responsible for the secretion of pineal peptides.

Animals↗

PubMed1997

Secretoneurin: a new neuropeptide in the rodent pineal gland.

The pineal gland of mammals is richly innervated by nerve fibres containing various peptides of central or sympathetic origin. In this study, we have investigated the presence, regulation and effect of secretoneurin (SN), a 33-amino-acid peptide discovered recently in the central and sympathetic nervous systems. The rat pineal gland contains about 34 fmol SN/pineal, although only 20% of the secretoneurin immunoreactivity (SN-IR) is the free peptide. SN-IR is localised in only a few nerve fibres found in the parenchyma of the gland and along the pineal stalk. In the rat pineal, SN-IR shows no midday/midnight differences but is significantly decreased (55%-65%) after superior cervical ganglionectomy or exposure to constant light. These observations suggest that, in the rat pineal, SN-IR originates partly from central areas and partly from the superior cervical ganglia. The pineal of the Syrian hamster contains much more SN-IR: 120 fmol SN-IR/pineal (about 20% being the free peptide). SN-IR is found both in nerve fibres and pineal cells. Some of the fibres run along the pineal stalk, indicating that they are of central origin, although a sympathetic origin cannot be ruled out. Pineal SN-IR is below detectable levels in the Siberian hamster. In cultured rat pinealocytes, SN significantly inhibits serotonin release and, to a lower extent, melatonin release.

Animals↗

PubMed1980

The kinetics of norepinephrine-induced stimulation of serotonin N-acetyltransferase in bovine pineal gland.

Fresh pineal explants were cultured in medium 199 containing 0.1 mg/ml of ascorbic acid, 2 mM glutamine, and 0.1% BSA in 95% O2 and 5% CO2 from 1 to 10 h. Norepinephrine (10 micrometers) increased serotonin N-acetyltransferase (NAT) activity from 2.36+ / -0.23 to 6.98+ / -0.46 pmol product produced/mg protein/min (unit), without influencing tryptophan hydroxylase, 5-hydroxytryptophan decarboxylase, monoamine oxidase, or hydroxyindole-O-methyltransferase. Dibutyryl cyclic AMP (1 mM) also stimulated NAT from 1.39+ / -0.12 to 4.33+ / -0.65 U. The norepinephrine-induced stimulation of NAT was blocked by GABA (10 micrometers), by dl-propranolol (20 micrometers), by cycloheximide (30 micrometers), by puromycin (20 micrometers), but not by actinomycin D (10 micrometers). Comparing the kinetics of native and stimulated NAT, the occurred changes in Vmax with regard to both substrates - tryptamine (from 0.885 to 3.44 U) and acetyl CoA (from 3.45 to 9.10 U) - without changes in Km with respect to both tryptamine (Km = 5 micrometers) and acetyl CoA (Km = 50 micrometers). The results of this investigation are interpreted to indicate that the norepinephrine-induced stimulation of NAT may be due to enhanced protein synthesis involving translational or post-translational events. Furthermore, the enhanced protein synthesis is coupled through activation of beta-receptor and cyclic AMP mediated actions in pineal gland. The precise interrelationship between GABA and norepinephrine in mediating and perhaps in controlling the biological events in the bovine pineal gland still awaits clarificaton.

Acetyltransferases↗

PubMed1982

Concentration of 5-methoxyindoles in the human pineal gland.

The pineal gland concentration of the four 5-methoxyindoles: melatonin, 5-methoxytryptamine, 5-methoxytryptophol and 5-methoxyindole-3-acetic acid, were measured by gas chromatography-mass spectrometry. The pineal glands were obtained from 11 subjects 2-3 hours post mortem. The concentration of 5-methoxytryptophol ranged from 4-93 pmoles/g, 5-methoxyindole-3-acetic acid from 79-560 pmoles/g and melatonin from 24-6860 pmoles/g. 5-methoxytryptamine was present only in trace amounts (0-12 pmoles/g). A variation over time of these compounds was not evident from the data obtained.

5-Methoxytryptamine↗

PubMed2003

Purification and immunohistochemical analysis of calcium-binding proteins expressed in the chick pineal gland.

The pineal gland is a site of melatonin production, of which intracellular calcium ions (Ca2+) are likely involved in various aspects. To investigate the identity of molecules responsible for the Ca2+-dependent processes in the pineal cells, we prepared a cellular extract from 2000 chick pineal glands and isolated a series of Ca2+-binding proteins by taking advantage of their Ca2+-dependent hydrophobic interaction with phenyl-Sepharose beads. The proteins identified by micro-sequencing analysis included calmodulin, neurocalcin, sorcin, annexin II and annexin V. Immunohistochemical analysis of the chick pineal sections revealed that both calmodulin and sorcin are expressed in the follicular and parafollicular pinealocytes. On the other hand, neurocalcin was expressed in a few neuron-like cells located predominantly in the parafollicular layer of the pineal follicle. These results suggest that calmodulin and sorcin may contribute to cellular functions in the chick pinealocytes.

Amino Acid Sequence↗

PubMed2003

Unravelling the role of pineal gland.

The pineal gland has been classically considered as a vestigial organ with mystic properties. With the development of new methodical experiments, its physiologic actions are unravelled vary depending on the level of the phylogenetic scale. Since the discovery of melatonin as the principal hormone of the pineal gland, is an important hormone involved in the control of circadian rhythms and other diverse biological functions. Recent metabolic, receptor and functional studies have discovered melatoninergic system(s) in living organisms, its organization, physiology and a role in some pathologic conditions. The melatonin-generating system is characterized by three basic features: (1) photosensitivity, (2) diurnal (or circadian) rhythmicity (with highest levels of melatonin production occurring at night in darkness), and (3) age-related decline in its activity.

Aging↗

PubMed2006

1800 MHz electromagnetic field effects on melatonin release from isolated pineal glands.

Isolated pineal glands of Djungarian hamsters (Phodopus sungorus) were continuously perifused by Krebs-Ringer buffer, stimulated with the beta-adrenergic receptor agonist isoproterenol to induce melatonin synthesis, and exposed for 7 hr to a 1800 MHz continuous wave (CW) or pulsed GSM (Global System for Mobile Communications)-modulated electromagnetic signal at specific absorption rate (SAR) rates of 8, 80, 800, and 2700 mW/kg. Experiments were performed in a blind fashion. Perifusate samples were collected every hour, and melatonin concentrations were measured by a specific radioimmunoassay. Both types of signal significantly enhanced melatonin release at 800 mW/kg SAR, while at 2700 mW/kg SAR, melatonin levels were elevated in the CW, but suppressed in the GSM-exposed pineal glands. As a temperature rise of approximately 1.2 degrees C was measured at 2700 mW/kg SAR, effects at this level are thermal. With regard to radiofrequency electromagnetic fields, the data do not support the 'melatonin hypothesis,' according to which nonthermal exposure suppresses melatonin synthesis.

Animals↗